Carbanions preparation

Allyllithium reagents have also been used in the synthesis of (Z)-y-alkoxyallylboronates 23 2 5. Stereoselectivity is excellent in these reactions since the (Z)-y-alkoxyallyl carbanions prepared by metalation of allyl ethers are stabilized by chelation. The (Z)-y-alkoxyallyl(diisopinocam-pheyl)boranes are prepared at low temperature by an analogous procedure and must be used at — 78 "C otherwise reaction diaslereoselectivity suffers owing to the facile isomerization to the -isomer26. 

Transmetallation of silyl enol ethers of ketones and aldehydes with Pd(II) generates Pd(II) enolates, which are usefull intermediates. Pd(II) enolates undergo alkene insertion and -elimination. The silyl enol ether of 5-hexen-2-one (241) was converted to the Pd enolate 242 by transmetallation with Pd(OAc)2, and 3-methyl-2-cyclopentenone (243) was obtained by intramolecular insertion of the double bond and -elimination [148], Formally this reaction can be regarded as carbopalladation of alkene with carbanion. Preparation of the stemodin intermediate 246 by the reaction of the silyl enol ether 245, obtained from 244, is one of the many applications [149]. Transmetallation and alkene insertion of the silyl enol ether 249, obtained from cyclopentadiene monoxide (247) via 248, afforded 250, which was converted to the prostaglandin intermediate 251 by further alkene insertion. In this case syn elimination from 250 is not possible [150]. However, there is a report that the reaction proceeds by oxypalladation of alkene, rather than transmetallation of silyl enol ether with Pd(OAc)2 [151]. 

Thus polystyryl carbanions and polyacrylonitrile carbanions prepared by anionic polymerization were reacted with cellulose acetate or tosylated cellulose acetate in tetrahydrofuran under homogenous reaction conditions. The carbanions displaced the acetate groups or the tosylate groups in a S v2-type nucleophilic displacement reaction to give CA-g-PS and CA-g-PAN. Mild hydrolysis to remove the acetate/tosylate groups furnishes the pure cellulose-g-polystyrene (Figure 3). 

The reaction of benzo[f]quinoline with methylsulphinyl carbanion prepared from dimetl lsulphoxide and sodium hydride leads to the 5-methyl and the 6-methyl derivatives in a 1 4 ratio. Although benzo[flquinoline-4-oxide gives a high yield of phenanthrene under these conditions, the carbanion generated using potassium t-butoxide as the base leads to alkylation at C-3 and to simultaneous deoxygenation (Y. Hamada and I. Takeuchi. J. org. Chem.. 1977. fa, 4209). 

The a-metallation of dialkyl chloromethylphosphonates with strong bases such as n-BuLi, x-BuLi, LDA, or LiTMP quantitatively gives dialkyl 1-lithio-l-chloromethylphosphonates. In contrast, the use of t-BuLi at low temperature leads to a mixture of H/Li and Cl/Li exchange products in a 9 1 ratio. In these conditions, the I-lithio-I-chloromethylphosphonate is stable only at low temperature. The same carbanion prepared using 2 eq of hindered amides such as LDA or LiTMP is stable at 0°C for 30 min without apparent degradation. The first equivalent of base effects the deprotonation, and the second probably stabilizes the resulting carbanion. ... 

Greengrass, C.W., and Hoople, D.W.T., Reaction of 4-acetoxy-2-azetidinone with tertiary carbanions. Preparation of 4-alkyl- and 4-alkyhdene-2-azetidinones, Tetrahedron Lett., 22, 1161, 1981. 

Diketones. This alkylation of ketimines has been extended to the synthesis of 1,4-diketones by use of a 2,3-dihalopropene as the alkylating reagent. The reaction is carried out with the carbanion, prepared as described above and then diluted with IHF at -60°. The resultant vinylic halide is then hydrolyzed with sulfuric acid at -20 to 0°. 

In a minor variation, the possession of an appropriately positioned carbonyl group by the phosphonic derivative, can lead to simultaneous expulsion of the phosphinoyl moiety with carbon-carbon double bond formation coupled with cyclization " . Although the ylide 157 can be alkylated on carbon (like the carbanion prepared by Arbuzov and Dunin), with simultaneous expulsion of the diethoxyphosphinoyl moiety (unlike the phosphory-lated carbanion), no reaction takes place between 157 and an aldehyde or ketone. ... 

This reaction showed high enantioselectivity even when (-)-sparteine was added after hthiation of the carboxamide. Also, the racemic lithium carbanion derived from the racemic tin precursor via metal exchange reaction, gave products with high enantioselectivity [Eq. (41)], whereas when the carbanion prepared from the corresponding chiral tin compound was reacted with an electrophile such as TMSCl without (-)-sparteine it yielded racemic product. These results indicate that the reaction of the lithiated 3-phenylpropionamide proceeds through an asymmetric substitution pathway. Furthermore, a warm-cool procedure and then reaction with a substoichiometric amount of an electrophile confirmed a dynamic thermodynamic resolution pathway for this reaction. 

A soln. of benzophenone in dry tetrahydrofuran added to a soln. of 1,3-dithiane 1-oxide carbanion prepared with n-butyllithium in hexane-tetrahydrofuran under... 

Dibromobicyclo [4.1.0] heptane allowed to react at room temp, with excess sodium methylsulfinyl carbanion prepared from Na or NaH in dimethyl sulfoxide 7-bromobicyclo [4.1.0] heptane (90% trans-isomer). Y 72%. F. e. s. 

Hydrolysis of Vinylogous Thioacetals. Carbanions prepared by lithiation of y-phenylthioallyl phenyl thioethers can serve as synthetic equivalents of /3-acyl vinyl anions. Umpolung of the usual electrophilic reactivity of 2-cyclohexenone is achieved by a sequence exploiting electrophilic capture of a hthiated vinylogous thioacetal and subsequent CuOTf-assisted hydrolysis (eq 57). Otherwise unfunctionalized vinylogous thioacetals can be hydrolyzed to enones by mercury(II) chloride in wet acetonitrile. However, the keto-substituted derivative in eq 57 gave only a 25% yield of enone by this method. A superior yield was obtained by CuOTf-assisted hydrolysis. ... 

A soln. of dry n-propyltriphenylphosphonium bromide in dimethyl sulfoxide treated at room temp, under Ng with methylsulfinyl carbanion prepared from NaH and dimethyl sulfoxide, after 5 min. the startg. hemiacetal in dimethyl sulfoxide added, and stirred 2.5 hrs. at room temp. 2-(cf -2-pentenyl)cyclopent-3-en-l-ol. Y 70%. P.A.Grieco, J. Org. Chem. 57, 2363 (1972). 

A soln. of methylsulfinyl carbanion prepared from NaH and dry dimethyl sulfoxide according to E. J. Corey and M. Chaykovsky, Am. Soc. 87, 1345 (1965) treated at 0° under Ng with diethyl chlorophosphate, then with a soln. of 4-di-methylaminobenzaldehyde in dry dimethyl sulfoxide, and stirred 3 hrs. at room temp. / -(4-dimethylaminostyryl) methyl sulfoxide. Y 70%. J. Almog and B. A. Weissman, Synthesis 1973, 164. 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

It looks as though all that is needed is to prepare the acetylenic anion then alkylate it with methyl iodide (Section 9 6) There is a complication however The carbonyl group m the starting alkyne will neither tolerate the strongly basic conditions required for anion formation nor survive m a solution containing carbanions Acetyhde ions add to carbonyl... 

Carboxylation (Section 19 11) In the preparation of a car boxyhc acid the reaction of a carbanion with carbon diox ide Typically the carbanion source is a Gngnard reagent... 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

Although most of the reactions of preparative importance involving the a-alkyl carbanions are usually carried out under controlled conditions with NHa /NHs being used as the base, a number of reactions using less severe conditions are known, both in the pyrazine and quinoxaline series. In the case of alkylquinoxalines, where an increased number of resonance possibilities exist, mildly basic conditions are usually employed in condensation reactions. 

Preparative routes to aziridines and 1-azirines are derived from cycloelimination processes in which one, and sometimes two, bonds are formed directly to the nitrogen atom (Scheme 1). For aziridines these include the two intramolecular cyclization pathways involving either nucleophilic displacement by the amine nitrogen (or nitrenium anion) on the /3-carbon (route a) or nucleophilic displacement by a /3-carbanionic centre on the amine nitrogen... 

The formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

In the discussion of the relative acidity of carboxylic acids in Chapter 1, the thermodynamic acidity, expressed as the acid dissociation constant, was taken as the measure of acidity. It is straightforward to determine dissociation constants of such adds in aqueous solution by measurement of the titration curve with a pH-sensitive electrode (pH meter). Determination of the acidity of carbon acids is more difficult. Because most are very weak acids, very strong bases are required to cause deprotonation. Water and alcohols are far more acidic than most hydrocarbons and are unsuitable solvents for generation of hydrocarbon anions. Any strong base will deprotonate the solvent rather than the hydrocarbon. For synthetic purposes, aprotic solvents such as ether, tetrahydrofuran (THF), and dimethoxyethane (DME) are used, but for equilibrium measurements solvents that promote dissociation of ion pairs and ion clusters are preferred. Weakly acidic solvents such as DMSO and cyclohexylamine are used in the preparation of strongly basic carbanions. The high polarity and cation-solvating ability of DMSO facilitate dissociation... 

Recently developed trifluoromethylatmg agents capable of transferring the trifluoromethyl group as a cation to strongly nucleophilic compounds such as carbanions and sulfur and phosphorus nucleophiles are prepared from o-biphenyl trifluoromethyl sulfoxide [164] and are shown in equation 141... 

NMR spectroscopy is ideal for detecting charged fluorinated intermediates and has been applied to the study of increasingly stable carbocation and carbanion species. Olah [164, 165] has generated stable fluorocarbocations m SbFj/SOjClF at low temperatures The relatively long-lived perfluoro-rerr-butyl anion has been prepared as both the cesium and tris(dimethylamino)sulfonium (TAS) salts by several groups [166, 167, 168], Chemical shifts of fluonnated carbocations and carbanions are listed m Table 23. 

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